Enzymes are playing an increasingly important role as catalysts in chemistry, due to their ability to catalyze highly selective transformations of chiral or polyfunctional molecules. See Whitesides, G. M., et al., Angew. Chem., Int. Ed. Engl. 24:617 (1985). Many reactions exist for which enzymes are unavailable, however. To address this situation, Pollack, S. J., et al., Science 234:1570 (1986), Jacobs, J. W., et al., J. Am. Chem. Soc. 109:2174 (1987), and Tramontano, A., et al., Science 234:1566 (1986) have demonstrated that the high binding specificity of the immune system can be exploited to develop new biological catalysts with tailored specificities. In addition, antibodies generated with catalytic groups in the binding site have been reported by Cochran, A. G., et al., J. Am. Chem. Soc. 110:7888 (1988), and Shokat, K. M., et al., Nature (London) 338:269 (1989); the generation of antibodies with cofactor binding sites has been reported by Shokat, K. M., et al., Angew. Chem., Int. Ed. Engl. 100:1227 (1988), and Iverson, B. L., et al., Science 243:1184 (1989); the generation of semisynthetic antibodies has been reported by Pollack, S. J., et al., Science 242:1038 (1988), and Pollack, et al., J. Am. Chem. Soc. 111:1929 (1989); use of the notion of approximation in the generation of antibodies has been reported by Napper, A. D., et al., Science 237:1041 (1987); and the notion of transition state stabilization as applied to the generation of antibodies has been reported by Pollack, S. J., et al., Science 234:1570 (1986), Jacobs, J. W., et al., J. Am. Chem. Soc. 109:2174 (1987), Tramontano, A., et al., Science 234:1566 (1986), Jackson, D. Y., et al., J. Am. Chem. Soc. 110:4841 (1988), and Hilvert, D., et al., Proc. Natl. Acad. Sci. U.S.A. 85:4953 (1988). The experimental data in the examples in this specification was published in Pollack, S. J., et al., J. Am. Chem. Soc. 111:5961 (1989).
The notion of transition state stabilization as applied to hydrolysis of esters has been reported by Janda, K. D., et al., Science 244:437 (1989), whose work has involved the generation of catalytic antibodies which stereospecifically hydrolyze unactivated esters of chiral alcohols. Other literature of potential relevance to this invention is that of Schechter, I., et al., Biochemistry 6:897 (1967), pertaining to the greater immunogenicity of D amino acids and their analogs as compared to the L counterparts.
A disclosure of a cleavage reaction which involves separation of a fluorescence-generating 2-aminobenzoyl group from a fluorescence-quenching 4-nitrobenzylamide group originally present on the same molecule, and the increase in fluorescence which results, is offered by Nishino, N., et al., J. Biol. Chem. 255:3482 (1980).